Storka Angela, Vcelar Brigitta, Klickovic Uros, Gouya Ghazaleh, Weisshaar Stefan, Aschauer Stefan, Bolger Gordon, Helson Lawrence, Wolzt Michael
Int J Clin Pharmacol Ther. 2015 Jan;53(1):54-65. doi: 10.5414/CP202076.
Experimental studies have shown that liposomal curcumin can exert a reduction in tumor growth in pancreatic and colorectal cancer. In this phase I clinical trial we investigated the pharmacokinetics, safety, and tolerability of intravenously administered liposomal curcumin in healthy subjects.
50 male and female participants were included in this randomized, placebo-controlled double-blind phase I dose escalation study. Subjects received a single dose of liposomal curcumin (10 - 400 mg/m2; n = 2 - 6 per group) or placebo over 2 hours intravenously.
Dose-dependent increases in the plasma concentrations of curcumin and its metabolite tetrahydrocurcumin (THC) were detected. After the end of drug infusion, curcumin and THC plasma concentrations decreased within 6 - 60 minutes below the limit of quantification. Mean urinary excretion was ~ 0.1% of total systemic clearance. Liposomal curcumin was tolerated well, but a transient red blood cell echinocyte formation with concomitant increase in mean cellular volume was observed at dosages ≥ 120 mg/m2.
Short-term intravenous dosing of liposomal curcumin appears to be safe up to a dose of 120 mg/m2. Changes in red blood cell morphology may represent a dose limiting sign of toxicity.
实验研究表明，脂质体姜黄素可降低胰腺癌和结直肠癌的肿瘤生长。在这项I期临床试验中，我们研究了静脉注射脂质体姜黄素在健康受试者中的药代动力学、安全性和耐受性。
50名男性和女性参与者被纳入这项随机、安慰剂对照、双盲的I期剂量递增研究。受试者在2小时内静脉接受单剂量的脂质体姜黄素（10 - 400mg/m²；每组n = 2 - 6）或安慰剂。
检测到姜黄素及其代谢产物四氢姜黄素（THC）的血浆浓度呈剂量依赖性增加。药物输注结束后，姜黄素和THC的血浆浓度在6 - 60分钟内降至定量限以下。平均尿排泄量约为全身总清除率的0.1%。脂质体姜黄素耐受性良好，但在剂量≥120mg/m²时观察到短暂的红细胞棘形细胞形成，同时平均细胞体积增加。
短期静脉注射脂质体姜黄素，剂量高达120mg/m²似乎是安全的。红细胞形态的变化可能是毒性的剂量限制标志。
